crossing96/oncoscreening huggingface dataset:
Amide Proton Transfer-Weighted Imaging in Assessing the Aggressive and Proliferative Potential of Bladder Cancer.	BACKGROUND: Ki-67 and human epidermal growth factor receptor 2 (HER2) are known oncogenes involved in bladder cancer (BCa) patient risk stratification. Preoperative assessment of their expression level can assist in clinical treatment decision-making. Recently, amide proton transfer-weighted (APTw) MRI has shown promising potential in the diagnosis of several malignancies. However, few studies reported the value of APTw imaging in evaluating Ki-67 and HER2 status of BCa. PURPOSE: To investigate the feasibility of APTw MRI in assessing the aggressive and proliferative potential regarding the expression levels of Ki-67 and HER2 in BCa. STUDY TYPE: Retrospective. SUBJECTS: 114 patients (mean age, 64.78 ± 11.93 [SD] years; 97 men) were studied. FIELD STRENGTH/SEQUENCE: APTw MRI acquired by a three-dimensional fast-spin-echo sequence at 3.0 T MRI system. ASSESSMENT: Patient pathologic findings, included histologic grade and the expression status of Ki-67 and HER2, were reviewed by one uropathologist. The APTw values of BCa were independently measured by two radiologists and were compared between high-/low-tumor grade group, high-/low-Ki-67 expression group, and high-/low-HER2 expression group. STATISTICAL TESTS: The interclass correlation coefficient, independent sample t-test, Mann-Whitney U test, Spearman's rank correlation, and receiver operating characteristic curve (ROC) analysis were used. P < 0.05 was considered statistically significant. RESULTS: Significantly higher APTw values were found in high-grade BCa patients (7.72% vs. 4.29%, P < 0.001), high-Ki-67 expression BCa patients (8.40% vs. 3.25%, P < 0.001) and HER2 positive BCa patients (8.24% vs. 5.40%, P = 0.001). APTw values were positively correlated with Ki-67 (r = 0.769) and HER2 (r = 0. 356) expression status. The area under the ROC curve of the APTw values for detecting Ki-67 and HER2 expression status were 0.883 (95% CI: 0.790-0.945) and 0.713 (95% CI: 0.592-0.816), respectively. DATA CONCLUSIONS: APTw MRI is a potential method to assess the biological and proliferation potential of BCa. TECHNICAL EFFICACY: Stage 2.	bladder
Molecular Pathology of Urothelial Carcinoma.	Urothelial carcinoma is characterized by the presence of a wide spectrum of histopathologic features and molecular alterations that contribute to its morphologic and genomic heterogeneity. It typically harbors high rates of somatic mutations with considerable genomic and transcriptional complexity and heterogeneity that is reflective of its varied histomorphologic and clinical features. This review provides an update on the recent advances in the molecular characterization and novel molecular taxonomy of urothelial carcinoma and variant histologies.	bladder
PC4 promotes bladder cancer progression and stemness by directly interacting with Sp1 to transcriptionally activate the Wnt5a/β-catenin pathway.	Bladder cancer is a common malignancy with a poor prognosis worldwide. Positive cofactor 4 (PC4) is widely reported to promote malignant phenotypes in various tumors. Nonetheless, the biological function and mechanism of PC4 in bladder cancer remain unclear. Here, for the first time, we report that PC4 is elevated in bladder cancer and is associated with patient survival. Moreover, PC4 deficiency obviously inhibited bladder cancer cell proliferation and metastasis by reducing the expression of genes related to cancer stemness (CD44, CD47, KLF4 and c-Myc). Through RNA-seq and experimental verification, we found that activation of the Wnt5a/β-catenin pathway is involved in the malignant function of PC4. Mechanistically, PC4 directly interacts with Sp1 to promote Wnt5a transcription. Thus, our study furthers our understanding of the role of PC4 in cancer stemness regulation and provides a promising strategy for bladder cancer therapy.	bladder
Predicting survival after brain metastases in patients with bladder cancer.	AIMS AND OBJECTIVES: Because of its rarity, limited data concerning brain metastasis (BM) from bladder cancer (BCa) are available, so this phenomenon remains unclear. We aimed to contribute to understanding this unique patient population's clinical behavior and outcomes. METHODS/MATERIALS: This retrospective cohort study included 27 BCa patients with BM treated at our Cancer Institute between April 2009 and December 2022. The time from initial diagnosis to BM and overall survival from BM diagnosis were calculated (Kaplan-Meier method). Cox regression was used to test key clinicopathologic associations. RESULTS: A total of 27 patients were included in the study (male/female = 23/4). The median patient age at BM diagnosis was 62.0 (47-79) years. The median interval from initial diagnosis to BM was 11.0 ± 2.59 (95 % CI, 5.91-16.08) months. Twenty (74.0 %) patients were diagnosed with BM by postsymptomatic imaging. The most common symptoms were headache-dizziness (n = 9, 33.3 %), seizure (n = 3, 11.1 %), hemiparesis (n = 2, 7.4 %), and vision defects (n = 2, 7.4 %). The most common sites of extracranial metastasis were the lung (n = 10, 52.6 %), bone (n = 7, 36.8 %), and lymph nodes (n = 6, 31.5 %). More than half of the patients (55.5 %) had multiple BMs. Eight (29.6 %) patients underwent surgery for BM. All of the patients received radiotherapy (RT) for BM (whole-brain radiotherapy (WBRT)/stereotactic radiotherapy (SRT) = 24/3), and eight patients received RT for the second time. Six patients were treated with systemic chemotherapy (CT) after BM. The median survival from BM was 3.0 ± 1.2 (95 % Cl, 0.4-5.5) months in the entire cohort. A low number of BMs (HR 0.270, 95 % CI 0.083-0.885; p = 0.031), surgery for BM (HR 0.174, 95 % CI 0.043-0.712; p = 0.015), CT after BM (HR 0.207, 95 % CI 0.057-0.755; p = 0.017), and better ECOG performance score (HR 0.248, 95 % CI 0.074-0.836; p = 0.025) were associated with better OS. CONCLUSIONS: Factors associated with improved survival in BCa patients with BM include a few brain lesions, intracranial resection, CT after BM, and better ECOG performance scores. Larger-scale prospective studies are needed to define the optimal management strategy further.	bladder
Impacts of Chlorine 1-3 ıon channels on localized bladder neoplasms.	Bladder tumors occur more frequently in men than in women and are the fourth most common malignancy after prostate, lung, and colon cancers. In this study, we examined the expression of chlorine ion channel 1 and chlorine ion channel 3 in localized bladder tumors according to their stage. We conducted a retrospective analysis of a prospective cohort study spanning from May 2018 to January 2020. This study involved a group of 55 patients who had been diagnosed with primary bladder cancer and underwent transurethral resection of bladder tumor under either general or spinal anesthesia. In addition, 30 patients who underwent cystoscopy due to etiology of hematuria and biopsies were taken from suspicious areas and whose results were normal were included as the control group. The collected samples were evaluated using real-time polymerase chain reaction in a medical genetics laboratory. In our study, it was observed that chlorine ion channel 3 gene expression increased significantly (P<0.001) in all cancer tissues compared to the control group, whereas no significant increase was found in chlorine ion channel 1 gene expression compared to the control group. The data obtained, especially for chlorine ion channel 3, are promising in terms of their use in the treatment of bladder tumors in humans.	bladder
Peimenine unleashes therapeutic promise in urothelial bladder cancer: inhibition of proliferation, induction of cell death and modulation of key pathways.	Peimenine (PEI) is a steroid alkaloid substance isolated from Fritillaria thunbergii bulbs. It has various pharmacological activities, such as relief from coughs and asthma, expectorant properties, antibacterial effects, sedative qualities, and anti-inflammatory properties. Notably, PEI can effectively inhibit the proliferation and tumor formation of liver cancer and osteosarcoma cells by inducing autophagic cell death. However, the precise effect and mechanisms of PEI on urothelial bladder cancer (UBC) cells remain uncertain. Thus, this study aims to investigate the impact of PEI on UBC cells both in vivo and in vitro. The IC(50) values of BIU-87 and EJ-1 cells after 48 h were 710.3 and 651.1 μg/mL, respectively. Additionally, PEI blocked the cell cycle in BIU-87 and EJ-1 cells during the G1 phase. Furthermore, it hindered the migration of BIU-87 and EJ-1 cells substantially. PEI significantly inhibited the tumor development of EJ-1 cells within the xenograft tumor model in vivo. Mechanically, PEI augmented the protein and mRNA expression of BIM, BAK1, and Cytochrome C (CYCS) in UBC cells. Taken together, PEI suppressed the proliferation of UBC cells both in vitro and in vivo by inducing cell death and cell cycle arrest, suggesting that PEI could be applied in the treatment of UBC.	bladder
Hematuria Cancer Risk Score with Ultrasound Informs Cystoscopy Use in Patients with Hematuria.	BACKGROUND: Hematuria is a cardinal symptom of urinary tract cancer and would require further investigations. OBJECTIVE: To determine the ability of renal bladder ultrasound (RBUS) with the Hematuria Cancer Risk Score (HCRS) to inform cystoscopy use in patients with hematuria. DESIGN, SETTING, AND PARTICIPANTS: The development cohort comprised 1984 patients with hematuria from 40 UK hospitals (DETECT 1; ClinicalTrials.gov: NCT02676180) who received RBUS. An independent validation cohort comprised 500 consecutive patients referred to secondary care for a suspicion of bladder cancer. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Sensitivity and true negative of the HCRS and RBUS were assessed. RESULTS AND LIMITATIONS: A total of 134 (7%) and 36 (8%) patients in the development and validation cohorts, respectively, had a diagnosis of urinary tract cancer. Validation of the HCRS achieves good discrimination with an area under the receiver operating characteristic curve of 0.727 (95% confidence interval 0.648-0.800) in the validation cohort with sensitivity of 95% for the identification of cancer. Utilizing the cutoff of 4.500 derived from the HCRS in combination with RBUS in the development cohort, 680 (34%) patients would have been spared cystoscopy at the cost of missing a G1 Ta bladder cancer and a urinary tract cancer patient, while 117 (25%) patients would have avoided cystoscopy at the cost of missing a single patient of G1 Ta bladder cancer with sensitivity for the identification of cancer of 97% in the validation cohort. CONCLUSIONS: The HCRS with RBUS offers good discriminatory ability in identifying patients who would benefit from cystoscopy, sparing selected patient cohorts from an invasive procedure. PATIENT SUMMARY: The hematuria cancer risk score with renal bladder ultrasound allows for the triage of patients with hematuria who would benefit from visual examination of the bladder (cystoscopy). This resulted in 25% of patients safely omitting cystoscopy, which is an invasive procedure, and would lead to health care cost savings.	bladder
TGF-β signalling limits effector function capacity of NK cell anti-tumour immunity in human bladder cancer.	BACKGROUND: Natural killer (NK) cells are important innate immunity players and have unique abilities to recognize and eliminate cancer cells, particularly in settings of antibody-opsonization and antibody-dependant cellular cytotoxicity (ADCC). However, NK cell-based responses in bladder cancers to therapeutic antibodies are typically immunosuppressed, and these immunosuppressive mechanisms are largely unknown. METHODS: Single cell RNA sequencing (scRNA-seq) and high-dimensional flow cytometry were used to investigate the phenotype of tumour-infiltrating NK cells in patients with bladder cancer. Further, in vitro, and in vivo models of this disease were used to validate these findings. FINDINGS: NK cells within bladder tumours displayed reduced expression of FcγRIIIa/CD16, the critical Fc receptor involved in ADCC-mediated cytotoxicity, on both transcriptional and protein levels. Transcriptional signatures of transforming growth factor (TGF)-β-signalling, a pleiotropic cytokine known for its immunosuppressive and tissue residency-inducing effects, were upregulated in tumour-infiltrating NK cells. TGF-β mediated CD16 downregulation on NK cells, was further validated in vitro, which was accompanied by a transition into a tissue residency phenotype. This CD16 downregulation was also abrogated by TGF-βR signalling inhibition, which could also restore the ADCC ability of NK cells subject to TGF-β effects. In a humanized mouse model of bladder cancer, mice treated with a TGF-β inhibitor exhibited increased ADCC activity compared to mice treated only with antibodies. INTERPRETATION: This study highlights how TGF-β-rich bladder cancers inhibit NK cell-mediated ADCC by downregulating CD16. TGF-β inhibition represents new avenues to reverse immunosuppression and enhance the tumoricidal capacity of NK cells in bladder cancer. FUNDING: The Guimaraes Laboratory is funded by a US Department of Defense-Breast Cancer Research Program-Breakthrough Award Level 1 (#BC200025), a grant (#2019485) awarded through the Medical Research Future Fund (MRFF, with the support of the Queensland Children's Hospital Foundation, Microba Life Sciences, Richie's Rainbow Foundation, Translational Research Institute (TRI) and UQ), and a grant (#RSS_2023_085) funded by a Metro South Health Research Support Scheme. J.K.M.W. is funded by a UQ Research Training Program PhD Scholarship and N.O. is funded by a NHMRC Postgraduate Scholarship (#2021932).	bladder
Pathological Extramural Venous Invasion in High-stage Urothelial Carcinoma of the Bladder has Shorter Locoregional Recurrence-free Survival.	Extramural venous invasion is an independent prognostic factor in colorectal cancers; the pathological identification of extramural venous invasion in bladder cancer remains unclear. By focusing on high-stage urothelial carcinoma of the bladder, we provide insights into the pathological identification of extramural venous invasion in this particular clinical context. Clinical and demographic details and pathological reports were extracted from electronic medical records. Histological sections were reviewed for the pathological identification of extramural venous invasion. Statistical analysis was done using SPSS version 23 software. Survival analysis was done using Kaplan-Meier method. In patients with available follow-up data, 62% (n = 21) exhibited pathologically evidenced extramural venous invasion, whereas 38% (n = 13) did not. The extramural venous invasion positive group showed trends toward more advanced and pathological staging and a higher occurrence of extra-nodal extension. Positive margins were more frequent in the extramural venous invasion positive group (33%) compared to the extramural venous invasion negative group (8%). However, these differences were not statistically significant. Notably, all instances of recurrence were in the extramural venous invasion positive group of patients. The extramural venous invasion positive group of patients showed a significantly shorter locoregional recurrence-free survival (P-value of 0.045). However, extramural venous invasion did not emerge as a significant factor in univariate analyses for recurrence-free survival. These findings highlight the potential role of extramural venous invasion as a prognostic factor in bladder cancer but underscore the need for further research with larger cohorts to confirm its significance.	bladder
Proteomic analysis of the urothelial cancer landscape.	Urothelial bladder cancer (UC) has a wide tumor biological spectrum with challenging prognostic stratification and relevant therapy-associated morbidity. Most molecular classifications relate only indirectly to the therapeutically relevant protein level. We improve the pre-analytics of clinical samples for proteome analyses and characterize a cohort of 434 samples with 242 tumors and 192 paired normal mucosae covering the full range of UC. We evaluate sample-wise tumor specificity and rank biomarkers by target relevance. We identify robust proteomic subtypes with prognostic information independent from histopathological groups. In silico drug prediction suggests efficacy of several compounds hitherto not in clinical use. Both in silico and in vitro data indicate predictive value of the proteomic clusters for these drugs. We underline that proteomics is relevant for personalized oncology and provide abundance and tumor specificity data for a large part of the UC proteome ( www.cancerproteins.org ).	bladder
The value of urinary exosomal microRNA-21 in the early diagnosis and prognosis of bladder cancer.	Bladder cancer (BC) poses high morbidity and mortality, with urinary exosomal microRNA (miR)-21 showing potential value in its diagnosis and prognosis, and we probed its specific role. We prospectively selected 116 BC patients and 116 healthy volunteers as the BC and control groups, respectively. BC urinary exosomal miR-146a-5p, miR-93-5p, miR-663b, miR-21, and miR-4454 relative expression levels were assessed. The correlations between clinical indexes and urinary exosomal miR-21, prognostic value of miR-21, and diagnostic value of the five candidate miRNAs, urine cytology, and miRNA joint diagnostic panel for BC and urinary exosomal miR-21, miR-4454, and urine cytology for Ta-T1 and T2-T4 stage BC were analyzed. Urinary exosomal miR-146a-5p, miR-93-5p, miR-663b, miR-21, and miR-4454 were highly expressed in BC patients. miR-146a-5p, miR-93-5p, miR-663b, miR-21, miR-4454, miRNA combined diagnostic panel, and urine cytology had certain diagnostic value for BC, with miR-21, miR-4454, and miRNA co-diagnostic panel showing the highest diagnostic value. Collectively, urinary exosomal miR-21 was closely related to Tumor-Node-Metastasis staging and grading in BC patients. Urinary exosomal miR-21 had high diagnostic value for BC and Ta-T1 and T2-T4 stage BC, and had high predictive value for BC poor prognosis, providing an effective indicator for the occurrence, development, and prognostic assessment of BC.	bladder
Immune features are associated with response to neoadjuvant chemo-immunotherapy for muscle-invasive bladder cancer.	Neoadjuvant cisplatin-based chemotherapy is standard of care for muscle-invasive bladder cancer (MIBC). Immune checkpoint inhibition (ICI) alone, and ICI in combination with chemotherapy, have demonstrated promising pathologic response (<pT2) in the neoadjuvant setting. In LCCC1520 (NCT02690558), a phase 2 single-arm trial of neoadjuvant chemo-immunotherapy (gemcitabine and cisplatin plus pembrolizumab; NAC-ICI) for MIBC, 22/39 patients responded (pathologic downstaging as primary outcome), as previously described. Here, we report post-hoc correlative analyses. Treatment was associated with changes in tumor mutational profile, immune gene signatures, and RNA subtype switching. Clinical response was associated with an increase in plasma IL-9 from pre-treatment to initiation of cycle 2 of therapy. Tumors harbored diverse predicted antigen landscapes that change across treatment and are associated with APOBEC, tobacco, and other etiologies. Higher pre-treatment tumor PD-L1 and TIGIT RNA expression were associated with complete response. IL-8 signature and Stroma-rich subtype were associated with improved response to NAC-ICI versus neoadjuvant ICI (ABACUS trial, NCT02662309). Plasma IL-9 represents a potential predictive biomarker of NAC-ICI response, while tumor IL-8 signature and stroma-rich subtype represent potential predictive biomarkers of response benefit of NAC-ICI over neoadjuvant ICI. Future efforts must include additional independent biomarker discovery and validation, ultimately to improve the selection of patients for ICI-related treatments.	bladder
Comprehensive Urinary Proteome Profiling Analysis Identifies Diagnosis and Relapse Surveillance Biomarkers for Bladder Cancer.	Bladder cancer (BCa) is the predominant malignancy of the urinary system. Herein, a comprehensive urine proteomic feature was initially established for the noninvasive diagnosis and recurrence monitoring of bladder cancer. 279 cases (63 primary BCa, 87 nontumor controls (NT), 73 relapsed BCa (BCR), and 56 nonrelapsed BCa (BCNR)) were collected to screen urinary protein biomarkers. 4761 and 3668 proteins were qualified and quantified by DDA and sequential window acquisition of all theoretical mass spectra (SWATH-MS) analysis in two discovery sets, respectively. Upregulated proteins were validated by multiple reaction monitoring (MRM) in two independent combined sets. Using the multi-support vector machine-recursive feature elimination (mSVM-RFE) algorithm, a model comprising 13 proteins exhibited good performance between BCa and NT with an AUC of 0.821 (95% CI: 0.675-0.967), 90.9% sensitivity (95% CI: 72.7-100%), and 73.3% specificity (95% CI: 53.3-93.3%) in the diagnosis test set. Meanwhile, an 11-marker classifier significantly distinguished BCR from BCNR with 75.0% sensitivity (95% CI: 50.0-100%), 81.8% specificity (95% CI: 54.5-100%), and an AUC of 0.784 (95% CI: 0.609-0.959) in the test cohort for relapse surveillance. Notably, six proteins (SPR, AK1, CD2AP, ADGRF1, GMPS, and C8A) of 24 markers were newly reported. This paper reveals novel urinary protein biomarkers for BCa and offers new theoretical insights into the pathogenesis of bladder cancer (data identifier PXD044896).	bladder
Testing the accuracy of a four serum microRNA panel for the detection of primary bladder cancer: a discovery and validation study.	BACKGROUND: Bladder cancer (BC) is one of the ten most common cancers worldwide with late detection and early age of diagnosis. There is abundant evidence that early detection and timely intervention can lead to a better prognosis of BC. Substantial evidence has indicated that microRNAs (miRNAs) are specific to different tumour types and are remarkably stable, indicating that serum miRNAs may serve as potential cancer diagnostic markers. This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary BC. METHODS: In this study, 18 miRNAs that were differentially expressed in BC were obtained from the PubMed or Gene Expression Omnibus database. Then, 18 BC-related-miRNAs were verified in screening and validation sets created using 56 (28 primary BC vs. 28 NCs) and 168 (84 primary BC vs. 84 NCs) serum samples, respectively. Quantitative reverse transcription-PCR (qRT-PCR) was performed to verify the identity of the differential miRNAs. A multi-miRNA panel with superior diagnostic performance was constructed. TCGA and KEGG databases were used to conduct the survival analysis and bioinformatics analysis, respectively. RESULTS: Six serum miRNAs (miR-221-5p, miR-181a-5p, miR-98-5p, miR-15a-5p, miR-222-3p, and miR-197-3p) were significantly aberrantly expressed in the BC patients, while four miRNAs from among them (miR-221-5p, miR-181a-5p, miR-15a-5p, miR-222-3p) were assembled into a panel that showed high diagnostic value (AUC = 0.875, 95% CI: 0.815 - 0.921; sensitivity: 82.14%; and specificity: 85.71%) based on the logistic regression analysis. The survival analysis showed that miR-181a-5p was closely associated with BC prognosis (Log-rank p-value < 0.05). CONCLUSION: The combination of the four miRNAs (miR-221-5p, miR-181a-5p, miR-15a-5p and miR-222-3p) may be a novel non-invasive serological biomarker for BC screening.	bladder